Journal of Cancer Research and Therapeutics Medknow Publications on behalf of the Association of Radiation Oncologists of India (AROI) ISSN: 0973-1482 EISSN: 1998-4138 Vol. 6, Num. 4, 2010, pp. 557-559

Journal of Cancer Research and Therapeutics, Vol. 6, No. 4, October-December, 2010, pp. 557-559

Case Report

Capecitabine-related intracranial hypotension syndrome mimicking dural metastasis in a breast cancer patient: Case report and review of the literature

Rusen Cosar-Alas¹, Aykan Alas², Alaattin Ozen¹, Bengu Denizli¹, Mert Saynak¹, Sernaz Uzunoglu³, Nurettin Aydogdu⁴, Hakan Karagol³, Cem Uzal¹, Zafer Kocak¹

¹ Department of Radiation Oncology, Trakya University Medical Faculty, Edirne, Turkey
² Private Edirne Radiology Center, Edirne, Turkey
³ Department of Medical Oncology, Trakya University Medical Faculty, Edirne, Turkey
⁴ Department of Physiology, Trakya University Medical Faculty, Edirne, Turkey

Correspondence Address: Rusen Cosar-Alas, Trakya University, Faculty of Medicine, Department of Radiation Oncology, 22030 Edirne, Turkey, rusencosar@yahoo.com

Code Number: cr10137

PMID: 21358101

DOI: 10.4103/0973-1482.77070

Abstract

Keywords: Capecitabine, mimicking dural metastasis, orthostatic headache, spontaneous intracranial hypotension syndrome

Introduction

Intracranial hypotension is known as spontaneous intracranial hypotension (SICH) or secondary to iatrogenic manipulation and breaching of dura, following a lumbar puncture or cranial/spinal surgery. ^[1],[2] The common MRI findings for this entity are the pachymeningeal enhancement, positive venous distention sign, ballooning of the vein of Galen, cerebellar ectopia. Dural gadolinium enhancement is often interpreted as dural metastasis which is seen in only 5% of patients with cancer. Therefore, distinctive diagnosis with SICH is very important in this particular group of patients. ^[3],[4]

In the presented case, diffuse regular pachimeningeal contrast enhancement, which mimicked static metastasis was obtained on cranial MRI, which was carried out to clarify the headache complaint during oral capecitabine treatment for metastatic breast cancer. Highly regular shape of pachymeningeal enhancement was suspicious for possible ICH on consultation by an experienced radiologist; therefore, the management of the patient was arranged as bed rest and intravenous dexamethasone treatment. Review of the literature revealed limited data because of the very little experience with oncologic patients suffering from intracranial hypotension.

Case Report

A fifty-eight-year old postmenopausal woman with breast cancer received 6 cycles of fluorouracil, adriamycin and cyclophosphamide chemotherapy and locoregional radiotherapy following a right modified radical mastectomy (invasive ductal carcinoma T3N3M0, estrogen and progesterone receptor (+)) in November 2003. While being followed under tamoxifen treatment, multiple bone metastases were developed on the second year. The treatment was rearranged as local RT, monthly zoledronic acid injection, and exemestane, and the patient was put on follow-up. On the 52 ^th month, docetaxel chemotherapy was launched due to liver metastasis. Abdominal CT evaluation after three cycles of chemotherapy showed progression of liver metastases. Her chemotherapy schedule was changed to oral capecitabine 2500 mg/m ² daily.

The patient reported intensive headache, nausea, vomiting, ptosis of left eyelid and lacrimation prior to fourth cycle of chemotherapy. She had ongoing lightheadedness since the first day, and on the twelfth day, she reported balance troubles. No hand-and-foot syndrome, diarrhea, or mucositis were reported. Laboratory test values including CBC, electrolytes, and thyroid function tests were within normal limits. Cranial MRI showed cerebellar and cerebral extensive subdural effusion and diffuse regular pachymeningeal gadolinium fixation [[Figure - 1]a, [Figure - 2]a, [Figure - 3]a]. With possible diagnosis of having pachymeningeal metastatic involvement or SICH, she was instructed to discontinue capecitabine, bed rest, fluid intake, and 16 mg dexamethasone treatment daily and the symptoms subsided over the next few days. A control cranial MRI was planned for fifteen days later. On her following visit, the patient had no complaints. Control cranial MRI revealed a decrease in regular opacification of dura, which definitely ruled out a metastatic involvement of the CNS [Figure - 1]b, [Figure - 2]b,[Figure - 3]b]. Another control cranial MRI was carried out on her fortieth day visit which showed complete remission in both of subdural effusion and regular pachymeningeal gadolinium fixation [[Figure - 1]c, [Figure - 2]c, [Figure - 3]c]. Oral capecitabine treatment was continued for another four cycles when her performance status improved.

Discussion

Intracranial hypotension syndrome gained popularity with the recent developments in the radiologic intervention modalities. Cranial MRI is essential for the exact diagnosis. The characteristic MRI finding is diffuse and continuous thickening of the dura in the supratentorial and infratentorial areas. Other cranial MRI findings include intracranial pachymeningeal thickening and post-contrast enhancement, subdural fluid collections and downward displacement or "sagging" of the brain. ^[5] Spinal MRI findings include collapse of the dural sac with a festooned appearance, intense epidural enhancement due to dilatation of the epidural venous plexus, and possible epidural fluid collections. ^[6] It is important for the radiologists to be familiar with this entity and to have an index of suspicion for the imaging findings associated with intracranial hypotension syndrome. This will aid in diagnosis and initiation of early treatment for this debilitating condition.

The doctrine states that intracranial blood volume and CSF volume are inversely correlated with each other within the cranium. ^[7] Accordingly, intracranial pressure caused by a decrease in CSF volume is balanced with an increase in blood volume, especially in the venous system of which capacity is high. This reflex mechanism protects fragile nerve tissue continuously against the bony structures, which surrounds it via a buffering system like blood or CSF. In cases with intracranial hypotension, volume increase observed in sinuses, over cortical venous structures and epidural plexuses supports this theory. However, in spontaneous cases, the first treatment is bed rest, fluid, and caffeine intake.

The pathogenesis of capecitabine-induced neurotoxicity is not well understood but it is most likely attributed to its metabolites, 5′-DFUR and fluorouracil. Both of these metabolites were shown to can cross the blood-brain barrier in a phase I study. ^[8] Capecitabine may cross the blood-brain barrier via the human concentrative nucleoside transporter in the form of 5′-DFUR, which was converted to fluorouracil due to the high concentration of thymidine phosphorylase in brain cells. ^[9]

The mechanism of drug action is that it mainly concentrates on epithelial tissue. The choroid plexus produces 80% of the CSF. The ependymal (epithelial) cells that line the ventricles of the brain fuse with the pia mater to form the choroid plexuses. Pia layer originates from two layers and each are composed of villi covered with single-layered cuboidal epithelium. ^[10] Decreased production of CSF is one of the causes of SICH etiology and this might be another route of SICH caused by oral capecitabine.

In prospective information of oral capecitabine, it is mentioned that 5% of side effects of the drug is headache. We hereby want to emphasize that patients who receive oral capecitabine medication should be checked for headache complaint, and evaluated with cranial MRI. Awareness of SICH by radiation oncologist, medical oncologist and radiologist in oncology patients is extremely important in order to prevent the patient from receiving unnecessary treatment by misinterpretation of diffuse and continuous dural gadolinium enhancement as central nervous system metastasis.

References

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